Journal article
Subretinal Delivery of AAV2-Mediated Human Erythropoietin Gene Is Protective and Safe in Experimental Diabetic Retinopathy
Investigative ophthalmology & visual science, Vol.55(3), pp.1519-1530
01 Mar 2014
PMID: 24508793
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
PURPOSE. We studied and developed a gene-based intraocular erythropoietin (EPO) therapy for diabetic retinopathy (DR), by which the applicability of neuroprotective therapy with favorable safety profile is attempted.
METHODS. Hematocrit (Hct) was measured in C57BL/6 mice after intramuscular injection of AAV2-CMV-hEPO virus. Diabetes was induced by intraperitoneal injection of streptozotocin in Sprague-Dawley (SD) rats. Subretinal or intravitreal injection was performed in SD rats and Dark Agouti (DA) rats. The human EPO (hEPO) concentration was measured with ELISA. Blood-retinal barrier (BRB) breakdown was measured with Evans blue permeation. Retinal function was evaluated with electroretinography (ERG). Retinal cell apoptosis was detected with TUNEL. Retinal thickness and cell counts were examined by light microscopy. Retinal vascular changes were evaluated with fundus fluorescein angiography (FFA) and confocal microscopy.
RESULTS. The serum hEPO was elevated 2 weeks after AAV2-CMV-hEPO virus injection, and Hct began to increase after 4 weeks. After subretinal injection, hEPO expressions in aqueous humor, vitreous, and retina followed a dose-and time-dependent manner. In the AAV2-CMV-hEPO-treated diabetic group, BRB was maintained, and retinal cell apoptosis was significantly reduced. The ERG results showed that the retinal function remained unchanged for at least one year after subretinal injection of AAV2-CMV-hEPO virus. Long-term expression of hEPO following subretinal injection of AAV2-CMV-hEPO virus did not induce neovascularization in retina and choroid.
CONCLUSIONS. The AAV2-CMV-hEPO gene therapy is safe, and it exerts long-term protective effects on diabetic retinas. Thus, the gene therapy by using AAV2-CMV-hEPO for DR is feasible.
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Details
- Title
- Subretinal Delivery of AAV2-Mediated Human Erythropoietin Gene Is Protective and Safe in Experimental Diabetic Retinopathy
- Creators
- Hua Xu - Shanghai Tenth People's HospitalLimei Zhang - Tongji UniversityLimin Gu - Shanghai Tenth People's HospitalLixia Lu - Tongji UniversityGuangping Gao - University of Massachusetts Medical SchoolWeiye Li - Drexel UniversityGuoxu Xu - Soochow Univ, Affiliated Hosp 2, Dept Ophthalmol, Suzhou, Peoples R ChinaJuan Wang - Tongji UniversityFurong Gao - Tongji UniversityJing-Ying Xu - Tongji UniversityJun Yao - Shanghai Tenth People's HospitalFang Wang - Shanghai Tenth People's HospitalJingfa Zhang - Tongji UniversityGuo-Tong Xu - Second Affiliated Hospital of Soochow University
- Publication Details
- Investigative ophthalmology & visual science, Vol.55(3), pp.1519-1530
- Publisher
- Assoc Research Vision Ophthalmology Inc
- Number of pages
- 12
- Grant note
- 31171419; 81000383 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) 20100072120051 / Research Fund for the Doctoral Program of Higher Education of China; Research Fund for the Doctoral Program of Higher Education of China (RFDP); Specialized Research Fund for the Doctoral Program of Higher Education (SRFDP) 2009KJ109 / Fundamental Research Funds for the Central Universities 2010QH04; 2010YF02 / Tongji University School of Medicine 2011DFB30010 / International Collaboration Fund 2011CB965102; 2012CBA01308; 2013CB967501 / National Key Basic Research Program of China; National Basic Research Program of China 11DZ1920904 / Science and Technology Commission of Shanghai; Science & Technology Commission of Shanghai Municipality (STCSM) 2012AA020906 / National High Technology Research and Development Program of China
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Ophthalmology [Historical]
- Identifiers
- 991019167671304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Ophthalmology